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IL-34 and protein-tyrosine phosphatase receptor type-zeta-dependent mechanisms limit arthritis in mice.
González-Sánchez, Hilda Minerva; Baek, Jea-Hyun; Weinmann-Menke, Julia; Ajay, Amrendra Kumar; Charles, Julia Forgan-Farnam; Noda, Masaharu; Franklin, Ruth Anne; Rodríguez-Morales, Patricia; Kelley, Vicki Rubin.
Afiliación
  • González-Sánchez HM; Renal Division, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA.
  • Baek JH; CONACyT - Centro de Investigación Sobre Enfermedades Infecciosas, Instituto Nacional de Salud Pública, Cuernavaca, Mexico.
  • Weinmann-Menke J; Renal Division, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA.
  • Ajay AK; School of Life Science, Handong Global University, Pohang, Gyeongbuk, Republic of Korea.
  • Charles JF; Department of Nephrology and Rheumatology, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.
  • Noda M; Renal Division, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA.
  • Franklin RA; Department of Orthopaedic Surgery, Brigham and Women's Hospital, Boston, MA, USA.
  • Rodríguez-Morales P; Homeostatic Mechanism Research Unit, Institute of Innovative Research, Tokyo Institute of Technology, Yokohama, Kanagawa, Japan.
  • Kelley VR; Department of Immunology, Harvard Medical School, Boston, MA, USA.
Lab Invest ; 102(8): 846-858, 2022 08.
Article en En | MEDLINE | ID: mdl-35288653
Myeloid cell mediated mechanisms regulate synovial joint inflammation. IL-34, a macrophage (Mø) growth and differentiation molecule, is markedly expressed in neutrophil and Mø-rich arthritic synovium. IL-34 engages a newly identified independent receptor, protein-tyrosine phosphatase, receptor-type, zeta (PTPRZ), that we find is expressed by Mø. As IL-34 is prominent in rheumatoid arthritis, we probed for the IL-34 and PTPRZ-dependent myeloid cell mediated mechanisms central to arthritis using genetic deficient mice in K/BxN serum-transfer arthritis. Unanticipatedly, we now report that IL-34 and PTPRZ limited arthritis as intra-synovial pathology and bone erosion were more severe in IL-34 and PTPRZ KO mice during induced arthritis. We found that IL-34 and PTPRZ: (i) were elevated, bind, and induce downstream signaling within the synovium in arthritic mice and (ii) were upregulated in the serum and track with disease activity in rheumatoid arthritis patients. Mechanistically, IL-34 and PTPRZ skewed Mø toward a reparative phenotype, and enhanced Mø clearance of apoptotic neutrophils, thereby decreasing neutrophil recruitment and intra-synovial neutrophil extracellular traps. With fewer neutrophils and neutrophil extracellular traps in the synovium, destructive inflammation was restricted, and joint pathology and bone erosion diminished. These novel findings suggest that IL-34 and PTPRZ-dependent mechanisms in the inflamed synovium limit, rather than promote, inflammatory arthritis.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Artritis Experimental / Artritis Reumatoide / Interleucinas / Proteínas Tirosina Fosfatasas Clase 5 Similares a Receptores Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Lab Invest Año: 2022 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Artritis Experimental / Artritis Reumatoide / Interleucinas / Proteínas Tirosina Fosfatasas Clase 5 Similares a Receptores Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Lab Invest Año: 2022 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos